IMMUNOHISTOCHEMICAL LOCALIZATION AND QUANTIFICATION OF GLIAL FIBRILLARY ACIDIC PROTEIN AND SYNAPTOSOMAL-ASSOCIATED PROTEIN (MOL. WT 25000) IN THE AGING HIPPOCAMPUS FOLLOWING ADMINISTRATION OF 5,7-DIHYDROXYTRYPTAMINE

Responses to injury in the ageing hippocampus were assessed utilizing the synaptic markers glial fibrillary acidic protein and synaptosomal- associated protein (mol. wt 25,000) following administration of the ne urotoxin, 5,7-dihydroxytryptamine, into the fimbria-fornix and cingulu m bundle to denervate serotonergic afferent input to the dorsal hippoc ampus. Age-dependent alterations in hippo campal immunohistochemical l ocalization of glial fibrillary acidic protein and synaptosomal-associ ated protein were evaluated in female Fischer 344 rats following serot onergic deafferentation with 5,7-dihydroxytryptamine. Across the lifes pan, as indicated by measurements taken at three, 18, 21 and 29 months , marked increases in glial fibrillary acidic protein, but not synapto somal-associated protein immunoreactivity, occurred throughout the hip pocampus at 21 and 79 months compared to three and 18 months. Followin g three weeks pretreatment with 5,7-dihydroxytryptamine (20 mu g total dose) or vehicle (0.1% ascorbic saline; 2 mu l total volume) infused in the fimbria-fornix/cingulum bundle, immunohistochemical analysis de monstrated marked increases of glial fibrillary acidic protein, but no t synaptosomal-associated protein, in the 18-month 5,7-dihydroxytrypta mine group compared to the 18-month vehicle and 3-month 5,7-dihydroxyt ryptamine groups. Additionally, a significant increase in glial fibril lary acidic protein concentration was found by enzyme-linked immunosor bent assay in the 18-month 5,7-dihydroxytryptamine group compared to t he 18-month vehicle and three-month 5,7-dihydroxytryptamine groups. Th ese results demonstrate that selective neurotoxicant damage of the hip pocampal serotonergic system differentially alters the expression of g lial fibrillary acidic protein. This approach may provide a valuable t ool to determine the ability of the hippocampus to respond to age-rela ted neurodegenerative injury. (C) 1998 IBRO. Published by Elsevier Sci ence Ltd.